Maintaining RAASi Treatment with Optimal Potassium Control

Phase III, Multicenter, Open-label, Randomized Clinical Trial to Evaluate Efficacy of Sodium Zirconium Cyclosilicate (Lokelma) Compared to Standard of Care to Manage Hyperkalemia in Patients With Chronic Kidney Disease (CKD)

This study is testing if adding a new medication can help people with chronic kidney disease safely continue their heart and blood pressure treatments without raising their potassium levels too high.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 78 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fundación para la Investigación del Hospital Clínico de Valencia (Academic / other)
• Locations: 5 sites (Alicante and 4 other locations)
• Trial ID: NCT06578533 on ClinicalTrials.gov

What this trial studies

This Phase III clinical trial aims to compare the effectiveness of Sodium Zirconium Cyclosilicate (CSZ) in maintaining treatment with renin-angiotensin-aldosterone system inhibitors (RAASi) and mineralocorticoid receptor antagonists (MRA) in patients with chronic kidney disease who are at risk of hyperkalemia. The study will involve 78 adult participants who will be randomly assigned to either continue their RAASi/MRA treatment with the addition of CSZ or have their treatment withdrawn or reduced. The primary outcome will be the proportion of patients achieving serum potassium levels below 5.5 mEq/L. The trial will be conducted across multiple sites in Spain over several visits for patient selection, randomization, and follow-up.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with chronic kidney disease stages 2-5 and elevated serum potassium levels between 5.5-6.5 mEq/L.

Not a fit: Patients who are on dialysis or have serum potassium levels outside the specified range may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could help patients maintain optimal RAASi/MRA treatment while effectively managing potassium levels, potentially improving their overall health outcomes.

How similar studies have performed: Other studies have shown promising results with similar approaches to managing hyperkalemia in patients on RAASi/MRA, indicating potential for success in this trial.

Eligibility criteria

Inclusion Criteria:

* Patients must present serum potassium levels of 5.5-6.5 mEq/L at patient selection visit (V0)
* Patients must present serum potassium levels of 5.0-6.5 mEq/L at randomization visit (V1).
* Provision of patient or legal representative informed consent prior to any study specific procedures.
* Individuals receiving background standard of care for HF and treated according to locally recognized guidelines. Specific treatment should include RAASi and/or MRA treatment at first consultation and at least should have been stable for ≥ 4 weeks at maximum tolerated doses.
* Patients with CKD not on dialysis (Stages 2-5: estimated glomerular filtration rate (eGFR) between 15-60 ml/min/1,73m2 or eGFR between 60-90 ml/min/ 1.73 m2 with albuminuria/creatinuria (\> 30 mg/g) in the previous three months). The estimated GFR can be reported by the laboratory or calculated by the researcher with serum creatinine, age, and sex (CKD-EPI equation).
* 18 years at the time of signing ICF.
* Negative pregnancy test (urine or serum) for female subjects of childbearing potential.
* Female subjects must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception (an acceptable method of contraception is defined as a barrier method in conjunction with a spermicide) for the duration of the study (from the time they sign ICF) and for 3 months after the last dose of SZC. In addition, oral contraceptives, approved contraceptive implant, long-term injectable contraception, intrauterine device, or tubal ligation are allowed. Oral contraception alone is not acceptable; additional barrier methods in conjunction with spermicide must be used.

Exclusion Criteria:

* Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site).
* Previous enrollment or randomization in the present study.
* HF due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy or uncorrected primary valvular disease.
* Current acute decompensated HF, hospitalization due to decompensated HF, myocardial infarction, unstable angina, stroke or transient ischemic attack within 12 weeks prior to enrollment.
* Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting or valvular repair/replacement within 12 weeks prior to enrollment or planned to undergo any of these operations after randomization).
* Implantation of a Cardiac Resynchronization Therapy (CRT) device or Implantable Cardioverter Defibrillator (ICD) within 12 weeks prior to enrollment or intent to perform atrial fibrillation ablation or to implant a CRT or ICD device.
* Previous cardiac transplantation or implantation of a ventricular assistance device or similar device, or transplantation or implantation expected after randomization
* Oropharingeal dysfunction that precludes normal swallow.
* Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method.
* Patients with amputated limbs or pacemaker devices will be excluded of bioimpedance analysis.
* Participation in another clinical study with an investigational product during the last 6 months.
* Patients with a known hypersensitivity to SZC or any of the excipients of the product.
* Treated with potassium binding resins such as sodium polystyrene sulfonate (SPS; e.g. Kayexalate®) or calcium polystyrene sulfonate (CPS; e.g. Resonium®) or the cation exchange polymer, patiromer sorbitex calcium (Veltassa®), within 7 days prior to the first dose of study drug.
* Judgment by the investigator that the subject should not participate in the study if the subject is unlikely to comply with study procedures, restrictions and requirements.
* Subjects with a family history of long QT syndrome, presence of cardiac arrhythmias or conduction defects that require immediate treatment, or a QTc (corrected QT interval) of ≥ 550 msec.
* History of QT prolongation associated with other medications that required discontinuation of that medications.
* Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted.

Where this trial is running

Alicante and 4 other locations

• Hospital General Universitario Dr. Balmis — Alicante, Spain (Recruiting)
• Hospital Universitario Vall d'Hebrón — Barcelona, Spain (Recruiting)
• Hospital Universitario 12 de Octubre — Madrid, Spain (Recruiting)
• Hospital Clínico Universitario de Valencia — Valencia, Spain (Recruiting)
• Hospital Universitario Doctor Peset — Valencia, Spain (Recruiting)

Study contacts

• Study coordinator: Jose Luis Górriz

Conditions Chronic Kidney Diseases